How Cannabis Affects Memory: It’s Not The Neurons

Getting mice stoned can actually result in important scientific discoveries. Research published in 2012 in Cell magazine reveals how marijuana impairs working memory, the short-term memory we use to hold on to and process thoughts. The classic example is of the stoner who forgets the point he was making, mid-sentence.

To study exactly how cannabis affects working memory in such a fashion, Giovanni Marsicano of the University of Bordeaux in France, Xia Zhang of the University of Ottawa Institute of Mental Health Research and their colleagues removed cannabinoid receptors from neurons in mice, reports Ruth Williams at Scientific American. These receptors are proteins that respond to marijuana’s chief psychoactive ingredient, THC (tetrahydrocannabinol).

Using microelectrodes implanted into the brains of rats, the researchers found that THC weakens the connections (synapses) between neurons in the hippocampus, an area of the brain crucial for memory formation.

The mice whose cannabinoid receptors had been removed from their neurons were just as forgetful as regular mice when given THC; that is to say, they were just as bad at memorizing the position of a hidden platform in a water pool. But when the cannabinoid receptors were removed from astrocytes, a type of glial cells, the mice could find the platform just fine while on THC.

The research reveals that the star-shaped astrocytes have a major role in working memory, with the results suggesting that the role of glia in mental activity has been overlooked. Glial cells were previously viewed as little more than the “glue” which supports neurons.

Although recent research has shown that glia are involved in many unconscious processes and diseases, this is one of the first studies to suggest that glia play a major role in conscious thought.

“Our study provides compelling evidence that astrocytes control neurons and memory,” Zhang said, reports Mo Costandi at Nature. “The supporting actor has become the leading actor.”

“It’s very likely that astrocytes have many more functions than we thought,” Marsicano said. “Certainly their role in cognition is now being revealed.”

“It’s always difficult to extrapolate from rodents to humans, but marijuana impairs working memory in both species, so I expect that similar mechanisms are involved,” Marsicano said.

The study shows an exciting link between astrocyte signaling and cognitive function, according to Ben Whalley, a pharmacologist at the University of Reading, UK. “It’ll be fascinating to investigate their consequences for endogenous cannabinoid signaling in normal brain function and in pathological states,” Whalley said.

Since THC’s pain-relieving property appears to work through neurons — unlike its effect on working memory — in theory, it might be possible to design THC-type drugs that target neurons, but not glia, thus offering pain relief without forgetfulness to patients who wish to maintain their cognitive capacity.

“But we still haven’t separated out the different effects of neuronal and astrocyte CB1 receptors, so the jury’s still out on the potential therapeutic effects of targeting the neuronal receptors,” Whalley said.

In the meantime, studies have shown that patients who use strains of marijuana containing high concentrations of the non-psychoactive but medicinal cannabinoid called cannabidiol (CBD) do not experience memory impairment, according to Nature. These strains are increasingly being used for medicinal purposes, especially with children; for example, the high-CBD strain Charlotte’s Web is being used by more and more families to stop the severe epileptic seizures associated with Dravet’s syndrome.

19 Comments

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Charles Waller
on December 13, 2013 at 8:40 am

As regards your closing statement, I am in complete accord. As per tolerance, we shall simply have to agree to disagree due to sparcity of
redundant, empirical data. The only research results I could find supporting your contention involved single cannabinoid content in
comparison to standard pharmacological compounds for treatment of specific conditions, and the data showed as many examples of lowered
tolerance as for increased depending on the condition and cannabinoid involved. I am skeptical of the results of studies with singular or synthetic cannabinoid content as they preclude the synergistic, or entourage, effect observed with herbal and whole plant extracts forms, as I am certain you are aware of based on your statements above. Thank you for the engaging and civil discussion. Please excuse the format, was replying on android pad while laptop ran scan and it dropped wifi, copied and pasted content from there doesn’t conform to this forum software. I have a love/hate relationship with the Acer A200 pad I bought to replace this crappy Toshiba laptop when my son’s laptop went belly up. It’s great for reading email, and simply looking at content, but it’s horrible for actually participating in thread discussions. I am glad you didn’t take the bait of sarcasm I typically use to weed out the less coherent commentators. Thank you, again.

coolduderino
on December 12, 2013 at 9:24 pm

Dude I’m only a few years behind you and my anecdotal experience (I prefer “inductive statistical sifting of ‘virtual survey’ results” from gazillions of observations and conversations) might as well be a masters degree and 30 years of research, but have it your way. A slight tolerance won’t stop anyone from enjoying recreational use, we’re talking about degrees of a thing, not the existence or lack thereof. Anyway, I’m deeply respectful of and enchanted by our species’ phytosymbiotic relationship with plant-evolved chemicals, have no fear.

Charles Waller
on December 11, 2013 at 5:45 pm

Yes, exactly as I thought. You know better than 170+ years of medical and scientific research based on your own anecdotal experience. As a primarily recreational user from 1971 to 1986, followed by 8 1/2 years of abstinence and 20 years since as a primarily medical user who still enjoys the recreational aspects, I have to call bullshit on your statements, especially “…every…long term recreational user knows it.”. I believe your comments simply demonstrate your lack of real knowledge on the subject and put you squarely in the camp of “feel good stoners” with little to no real knowledge about the most beneficial plant known to humanity.

coolduderino
on December 11, 2013 at 4:56 pm

“Excessive use and quality material”…True, but not a very unusual circumstance. Indeed, most users accept some degree of tolerance in exchange for frequent use of quality material. Smoking schwag once or twice a week doesn’t appeal to most users. True purely medicinal use is a rare circumstance indeed, but in your model of moderate self titration for specific non-recreational effects, it is less likely a person will develop a severe tolerance, but tolerance is real and not rare, whatever the particular cause in a specific case. I don’t need a study to demonstrate this, any…make that every… long term recreational user knows it.

Charles Waller
on December 11, 2013 at 4:33 pm

Individual biochemistry and psychology are indeed motivators of behavior and valid points. I’m sorry if inclusion of my own anecdotal experience concerning an individual that meets all the criteria cited by us both prompted you to dismiss the valid points I made regarding the activity which leads to developing a tolerance. Biochemistry may require a person to consume more or less to achieve the desired effect, and individual psychology may cause them to consume in an excessive manner, but actual tolerance to cannabinoid content has been repeatedly demonstrated to occur under limited circumstances and is indicative of either excessive use or quality of material. Unlike toxic substances like alcohol or cocaine, phytocannabinoids are analogous to endogenous cannabinoids and superfulous amounts are typically discarded by the body. If you have solid empirical evidence to support your statement I would be happy to read it. I can supply same supporting my opinion if you have yet to locate and read any, as I have as yet found any research results to support your contention. Have a nice day.

coolduderino
on December 11, 2013 at 2:34 pm

I think some people attain tolerance faster than others for lots of reasons, including their natural genetic biochemistry and even personality profile. Some people just don’t recognize when they are high, even when others can tell based on their behavior. In any case, your personal experience is as irrelevant as the previous poster’s.

Please don’t believe everything you read and on television etc. Governments lie to their people. I have found that following what is said many times will expose itself to be true or not true. Sorry but the doctor is talking out of the side of his mouth and if you read he doesn’t know what he is saying and states it. I will clarify this article of TOK “How Cannabis Affects Memory: It’s Not The Neurons”

I will tell you what I know about the government. The government does not want the people to use marijuana. The people are programmed a world through an iron curtain controlled mass media with very specific thoughts to think and not to think. A very small portion of the brain is used by the citizen. Most is stored in memory and the abusing authority wants to keep it that way.

“What the Doctor is trying to say is under the influence of marijuana other portions of the brain are being used and when we pop into it, nothing yet is there!” Kindness of the listener has a duty to tell the speaker what they said prior and hopefully the subject can then be completed. That is just common courtesy.

Government want programmed citizens and to not question what they say agreeing with them unconsciously. Under the influence of marijuana other and better answers come to mind; even discovering ulterior motives for the reason the government is proposing and want the people to swallow down what they say whole and not in part.

Charles Waller
on December 6, 2013 at 5:42 am

I doubt your singular anecdotal experience sets the standard for scientific research. You may just be buying hemp cannabis treated with synthetic cannabinoids. Or possibly just poor grade with very low levels of THC. Controlling for variables is part of the scientific process, and the lack of control over illicit substances sold without quality control or purity standards eliminates your personal experience as relevant data for anyone but yourself. If you build up a tolerance to what you are smoking there are typically only 2 causes, either low grade cannabis, as mentioned previously, or excessive use. I have seen the former in an acquaintance who smoked enormous joints of very high quality cannabis constantly, regardless whether he had reached “saturation” or not. Since the variety was a hybrid with elevated levels of CBD, and he was prone to early harvesting, his behavior was self-defeating for the purpose of “intoxication”. Some people simply aren’t satisfied and too much is never enough. I consumed the same variety during the same time period and never experienced any increase in tolerance – almost certainly because I was self-titrating for pain & muscle spasticity while he was simply “getting high”.

cannabisdoc
on December 6, 2013 at 12:10 am

i dont think they are going to start slicing up human brains anytime soon sir

Beth Kiser
on December 5, 2013 at 11:20 pm

I had a bad brain injury 12 years ago and drs told me not to smoke that it would put me back in a coma and my brain is working better than it ever did 10 years ago and I think weed is to blame for that but Im not to sure cause Ive been clean for a few months

adam
on December 5, 2013 at 9:04 pm

I’m not forgetful when on it so maybe you should switch from mice to humans cause you know we have bigger brains and mice are totally different than we are lmao …and you call your self scientist …. also you build a tolerance up to it over time to a point to where you can’t even get high anymore!!

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